Admin Supplement: Brain Glycogen - Metabolism, Mechanisms, and Therapeutic Potential

Grants and Contracts Details


The standard of care for AD patients has only incrementally improved in the last decade with AD patients still suffering from a slow and inevitable decline in cognitive function and neurodegeneration. Glucose hypo-metabolism occurs in almost all AD cases and defining the mechanism could provide a novel AD therapeutic target. Our compelling preliminary data suggest aberrant AD-PGBs modulate glucose metabolism and we have developed VAL-0417 as a pre-clinical treatment to ablate the AD-PGBs. Recent human studies suggest that age-related cognitive decline, AD risk, and preclinical AD amyloid plaque pathology are more strongly associated with increased sleep fragmentation than with total sleep loss. Fragmentation of the daily sleep-wake rhythm is associated with greater risk of incident AD and earlier cognitive decline in older humans, and this association remains even after controlling for the total daily rest time, medical history, and demographic factors. Preclinical AD pathology is also associated with fragmentation of the daily rest-activity rhythm in middle-aged and older humans. Additionally, our preliminary data demonstrate that AD-related mouse models, including 5xFAD, exhibit increased Aβ accumulation and neuroinflammation with sleep fragmentation. AD hypo-metabolism is likely connected to AD sleep dysfunction, but the mechanistic nature of this association is unknown. We postulate that the Gentry and Murphy labs can capitalize on our individual areas of expertise to understand the integrative physiology of sleep and sleep disruption on AD using cutting-edge technology, including metabolomics and RNAseq, while evaluating a putative novel target for AD prevention. Per NOT-NS-21-040, Drs. Gentry and Murphy have not previously collaborated or published together.
Effective start/end date5/15/204/30/22


  • National Institute of Neurological Disorders & Stroke


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